Young Indigenous children in North America suffer from a higher degree of severe early childhood caries (S-ECC) than the general population, leading to speculation that the etiology and ...characteristics of the disease may be distinct in this population. To address this knowledge gap, we conducted the first microbiome analysis of an Indigenous population using modern molecular techniques. We investigated the caries-associated microbiome among Canadian First Nations children with S-ECC. Thirty First Nations children <72 mo of age with S-ECC and 20 caries-free children were recruited in Winnipeg, Canada. Parents or caregivers completed a questionnaire on general and dental health, diet, and demographics. The plaque microbiome was investigated by sequencing the 16S rRNA gene. Sequences were clustered into operational taxonomic units and taxonomy assigned via the Human Oral Microbiome Database, then analyzed at the community level with alpha and beta diversity measures. Compared with those who were caries free, children with S-ECC came from households with lower income; they were more likely to live in First Nations communities and were more likely to be bottle-fed; and they were weaned from the bottle at a later age. The microbial communities of the S-ECC and caries-free groups did not differ in terms of species richness or phylogenetic diversity. Beta diversity analysis showed that the samples significantly clustered into groups based on caries status. Twenty-eight species-level operational taxonomic units were significantly different between the groups, including Veillonella HOT 780 and Porphyromonas HOT 284, which were 4.6- and 9-fold higher, respectively, in the S-ECC group, and Streptococcus gordonii and Streptococcus sanguinis, which were 5- and 2-fold higher, respectively, in the caries-free group. Extremely high levels of Streptococcus mutans were detected in the S-ECC group. Overall, First Nations children with S-ECC have a significantly different plaque microbiome than their caries-free counterparts, with the S-ECC group containing higher levels of known cariogenic organisms.
Severe early childhood caries (S-ECC) is a multifactorial disease that can lead to suffering and reduced oral health–related quality of life in young children. The bacterial and fungal composition of ...dental plaque and how children’s sex is associated with S-ECC are largely unknown. In this study, V4-16S rRNA and ITS1 rRNA gene amplicon sequencing was used to compare the plaque bacteriome and mycobiome of children <72 mo of age: 40 with S-ECC (15 males, 25 females) and 40 caries-free (19 males, 21 females). Health- and nutrition-related questionnaire data were also investigated. This study aimed to analyze potential sex-based differences in the supragingival plaque microbiota of young children with S-ECC and those caries-free. Behavioral and nutritional habit differences were observed between children with S-ECC and those caries-free and between male and female children. Overall, higher levels of Veillonella dispar, Streptococcus mutans, and other bacterial species were found in the S-ECC group as compared with caries-free controls (P < 0.05). A significant difference in the abundance of Neisseria was observed between males and females with S-ECC (P < .05). Fungal taxonomic analysis showed significantly higher levels of Candida dubliniensis in the plaque of children with S-ECC as compared with those caries-free (P < 0.05), but no differences were observed with Candida albicans (P > 0.05). Significant differences in the relative abundance of Mycosphaerella, Cyberlindnera, and Trichosporon fungal species were also observed between the caries-free and S-ECC groups (P < 0.05). Machine learning analysis revealed the most important bacterial and fungal species for classifying S-ECC versus caries-free. Different patterns of crosstalk between microbial species were observed between male and female children. Our work demonstrates that plaque microbiota and sex may be important determinants for S-ECC and could be factors to consider for inclusion in caries risk assessment tools.
Background:
The use of silver diamine fluoride (SDF) as a nonsurgical caries management product is growing. Evidence suggests that SDF is very successful in arresting caries. However, a common ...concern with SDF treatment is the unaesthetic black staining. The purpose of this qualitative study was to determine parents’ views following their children’s treatment with SDF to manage severe early childhood caries (ECC).
Method:
Parents were interviewed as part of a mixed-method study of SDF to arrest severe ECC. Children with caries lesions in primary teeth were treated with 2 applications of 38% SDF, followed by fluoride varnish. Semistructured in-person and phone interviews were conducted with 19 parents of children in the study. Data were transcribed verbatim and manually coded and uploaded to NVivo 12 for further coding analysis.
Results:
None of the parents had previously heard about SDF, and they learned about it from the study dentist. Although parents trusted the dentist’s information on SDF, they welcomed additional evidence, especially relating to product safety and effectiveness. Some parents were minimally concerned with the black staining caused by SDF treatment. It was more important that SDF arrested caries progression, minimized pain and sensitivity, and prevented dental infection. However, some parents expressed concerns related to the unaesthetic black staining. Interestingly, many parents indicated that their children were not overly concerned with the black staining. A majority of parents said that they would recommend the treatment to others.
Conclusion:
This is the first qualitative study involving parents of children who were treated with SDF. Most parents were accepting of SDF as a nonsurgical treatment to arrest caries and minimize dentinal sensitivity secondary to caries, although some expressed concern about the black staining in anterior teeth. It is important to adequately inform parents of the negative aesthetic consequences and obtain informed consent before treatment.
Knowledge Transfer Statement:
This qualitative study revealed that many parents of children with severe ECC are accepting of SDF as a nonrestorative caries management option, despite the black staining of caries lesions. Dental professionals need to be aware of these parental concerns and obtain written informed consent prior to treatment. Parents also requested more information and resources on SDF on its benefits, effectiveness, and any associated risks.
The cause of reduced Tamm-Horsfall protein excretion in patients suffering from uric acid diathesis is still unknown. Our investigation was conducted based on the hypothesis that the solubility of ...uric acid is increased by Tamm-Horsfall protein and that an increased uric acid content in the urine might cause a decrease in Tamm-Horsfall protein. In 20 patients with uric calculi the excretion of Tamm-Horsfall protein, uric acid, calcium, and citrate was measured. 65% of the patients had pure uric acid stones (group I) and 35% showed mixed stones with at least 30% of uric acid (group II). Reduced Tamm-Horsfall protein excretion was found in 63% of the patients of group I and in 43% of the patients of group II. The excretion of Tamm-Horsfall protein was significantly reduced in pure uric acid stone formers compared to normal subjects (p < 0. 0001). The excretion of uric acid was elevated in 61% of the patients of group I and in 86% of the patients of group II. There was no significant correlation between Tamm-Horsfall protein excretion and uric acid excretion (r = 0.2139). Calcium excretion was elevated in 57% of the patients with mixed stones. The excretion of citrate was reduced in almost all of the patients of groups I and II. Our results do not support the hypothesis that an increased content of uric acid in the urine causes a decrease in Tamm-Horsfall protein. In our opinion the lower excretion of Tamm-Horsfall protein in some of the stone patients might be caused by damage in the distal tubular epithelium. Moreover, it has to be supposed that there are defects both in the distal and the proximal tubule in patients prone to develop uric acid calculi.
We report on a prospective DNA cytophotometric study of 66 patients with renal tumors, 61 of whom had renal cell carcinoma (RCC) (pT1-pT4, G1-G3). 16 of the patients had a metastasis at the time of ...diagnosis. Cell material from 1-5 specimens of each tumor was analyzed for intratumoral heterogeneity. The aim of the study was to evaluate the prognostic value of the following DNA parameters: DNA ploidy, DNA grade of malignancy (DNA MG), mean DNA, DNA index, 2c deviation index (2cDI), and 5c exceeding rate (5cER). In this study 21% of the tumors were non-aneuploid, 79% were aneuploid; however, it proved possible to diagnose 38% of the total collective as aneuploid only by analyzing several tumor areas. In five of 61 RCC patients who died during an observation period of 42 months, at least one area of the primary tumor was aneuploid. Aneuploid primary tumors also accompanied the development of metastases and recurrent tumors in four of the 61 RCC patients. Only DNA 2cDI was found to have a significantly positive clinical correlation with metastasis (r = 0.261) during the clinical course. This was not true, however, for the histopathologic parameters. Significantly positive correlations were found between the tumor stages and the following DNA parameters: mean DNA, DNA index, and 5cER. Histopathologic tumor grading showed a significantly positive correlation with DNA MG, mean DNA, and 5cER. Statistically, the mean values of all evaluated parameters were significantly higher in metastasizing and recurrent RCCs than in non-metastasizing carcinomas (p < 0.05; t-test). DNA cytophotometry cannot substitute histopathologic prognosis. However, the analysis of various DNA parameters helps considerably in evaluating both the malignant potential of kidney tumors and the benign parenchyma of tumor-bearing kidneys.
Severe Early Childhood Caries (S-ECC) is an aggressive form of tooth decay in preschool children affecting quality of life and nutritional status. The purpose was to determine whether there is an ...association between Body Mass Index (BMI) and S-ECC.
Children with S-ECC were recruited on the day of their slated dental surgery under general anesthesia. Age-matched, caries-free controls were recruited from the community. All children were participating in a larger study on nutrition and S-ECC. Analysis was restricted to children ≥ 24 months of age. Parents completed a questionnaire and heights and weights were recorded. BMI scores and age and gender adjusted BMI z-scores and percentiles were calculated. A p-value ≤ 0.05 was significant.
Two hundred thirty-five children were included (141 with S-ECC and 94 caries-free). The mean age was 43.3 ± 12.8 months and 50.2 % were male. Overall, 34.4 % of participants were overweight or obese. Significantly more children with S-ECC were classified as overweight or obese when compared to caries-free children (p = 0.038) and had significantly higher mean BMI z-scores than caries-free children (0.78 ± 1.26 vs. 0.22 ± 1.36, p = 0.002). Those with S-ECC also had significantly higher BMI percentiles (69.0 % ± 29.2 vs. 56.8 % ± 31.7, p = 0.003). Multiple linear regression analyses revealed that BMI z-scores were significantly and independently associated with S-ECC and annual household income as were BMI percentiles.
Children with S-ECC in our sample had significantly higher BMI z-scores than caries-free peers.
The different subgroups of hypercalciuria cannot be separated clearly by the Pak calcium-load test. To improve the diagnosis and therapy we examined all relevant parameters of calcium metabolism in ...32 patients with calcium urolithiasis and hypercalciuria (> 6.25 mmol/day). We also conducted bone mineral density measurements as well as the Pak calcium-load test. In most cases the pathophysiological constellations which Pak takes as the basis for his classification of hypercalciuria could not be shown. To date, diagnostics only insufficiently explains the genesis of hypercalciuria (except pHPT). As a consequence, a therapeutic problem arises: a low-calcium diet should not be generally recommended, since some patients may develop osteopenia. From our investigation the following diagnostic and therapeutic conclusions can be drawn: (1) Hypercalciuria in primary hyperparathyroidism should be treated by surgical removal of the adenoma. (2) The parathormone-independent osteogenic form should be treated with thiazides. (3) Hypercalciuria with increased 1.25-dihydroxyvitamin D should be treated by low-calcium diet.
Contribution of host-related cytokine release in the course of pretransplant conditioning to early tissue damage and induction of acute graft-versus-host disease (GVHD) after allogeneic bone marrow ...transplantation (BMT) has been shown in experimental models. We performed a clinical phase l/ll trial applying a monoclonal antibody neutralizing human tumor necrosis a (TNFα) during pretransplant conditioning as additional prophylaxis in high-risk patients admitted to allogeneic BMT; TNFα serum levels and clinical courses in 21 patients receiving anti-TNFα prophylaxis were compared with data from 22 historical controls. Absence of significant release of TNFα in the period of busulphan (BUS) treatment, but significant induction of TNFα by total body irradiation (TBI) and cyclophosphamide (CY) conditioning were correlated with significantly earlier onset of acute GVHD in patients receiving TBI/CY regimens as compared with BUS/CY-treated patients. Prophylactic application of monoclonal anti-TNFα seemed to postpone onset of acute GVHD from day 15 to day 25 (P < .05) after TBI/CY and from day 33 to day 53 after BUS/CY (P < .10) conditioning. Application of monoclonal anti-TNFα in low and intermediate doses was safe and not associated with an increased incidence of infectious or hematologic complications. Thus, our data provide indirect and direct evidence for involvement of conditioning-related cytokine release in induction of early acute GVHD in the clinical setting and support further investigation of this novel approach in randomized trials.
Blast crisis is one of the remaining challenges in chronic myeloid leukemia (CML). Whether additional chromosomal abnormalities (ACAs) enable an earlier recognition of imminent blastic proliferation ...and a timelier change of treatment is unknown. One thousand five hundred and ten imatinib-treated patients with Philadelphia-chromosome-positive (Ph+) CML randomized in CML-study IV were analyzed for ACA/Ph+ and blast increase. By impact on survival, ACAs were grouped into high risk (+8, +Ph, i(17q), +17, +19, +21, 3q26.2, 11q23, -7/7q abnormalities; complex) and low risk (all other). The presence of high- and low-risk ACAs was linked to six cohorts with different blast levels (1%, 5%, 10%, 15%, 20%, and 30%) in a Cox model. One hundred and twenty-three patients displayed ACA/Ph+ (8.1%), 91 were high risk. At low blast levels (1-15%), high-risk ACA showed an increased hazard to die compared to no ACA (ratios: 3.65 in blood; 6.12 in marrow) in contrast to low-risk ACA. No effect was observed at blast levels of 20-30%. Sixty-three patients with high-risk ACA (69%) died (n = 37) or were alive after progression or progression-related transplantation (n = 26). High-risk ACA at low blast counts identify end-phase CML earlier than current diagnostic systems. Mortality was lower with earlier treatment. Cytogenetic monitoring is indicated when signs of progression surface or response to therapy is unsatisfactory.
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